The objectives of the proposed project are to characterize the properties of the different types of serotonin (5-hydroxytryptamine, 5-HT) receptors in the mammalian central nervous system and to explore the possibility that additional subtypes of these exist. This will be done using in vitro binding assays utilizing various ligands, such as 3H-5-HT, 3H-spiperone, and 3H-LSDd, which are known to label certain populations of serotonin receptors, and then the properties of the receptors as measured by this technique will be compared to the properties of 5-HT receptors which regulate adenylate cyclase activity (both high- and low-sensitivity systems) and which regulate the release of 5-HT itself. A major emphasis of this work will be the pahrmacological characterization of these sites in an attempt to determine the structural requirements for various 5-HT agonists and antagonists to discriminate between different types of serotonin receptors, expecially with respect to the different populations of 3H-5-HT binding sites which have recently been described. The different types of 5-HT receptors will also be evaluated and compared according to their subcellular distributions (using differential and density gradient centrifugation techniques), and their regional distributions. In addition the receptors will be characterized according to their responses to physical changes in their milieu, such as ionic composition, temperature, pH, detergents, etc. Once these groups of receptors are classified and characterized, it is hoped that more specific drugs can be designed for affecting particular 5-HT receptors so that the actions of 5-HT in the central nervous system can be more carefully studied, and perhaps eventually more effective therapeutic agents can be designed for treating certain behavioral or mental disorders that are thought to be linked to abnormal serotonergic function.